Dr.

Scott Napper

Professor, Department of Biochemistry

Senior Research Scientist, Vaccine and Infectious Disease
Organization-International Vaccine Center
University of Saskatchewan
[email protected]
306-956-1546
 Chapter 1: Biochemistry and the Unity of Life

Objectives:
• Contrast basic differences and similarities between prokaryotes and
eukaryotes.
• Appraise the chemical foundations of life and discriminate basic chemical
functional groups.
• Identify chiral carbons and explain how stereochemistry relates to
biochemistry.
• Explore the major classes of biomolecules, including description of the
unique building blocks and linkages within each class.
• Explain life from a thermodynamic perspective.
• Summarize the genetic basis of living organisms with consideration to how
this relates to evolution.

Text Readings:
Stryer 2nd or 3rd Edition, All of Chapter 1
Biochemistry is:

• the study of life at the molecular level.

• the application of the principles of chemistry to

explain biology.

• the common sets of reactions and principles that

underlie all living organisms.

• the study of the molecular logic of life.

 Unity of Biochemistry/Unity of Life
• In spite of considerable differences in their size and complexity, all living
organisms are remarkably uniform at the molecular level.
• All organisms use:
• a common repertoire of building blocks to create common categories
of biomolecules (nucleic acids, proteins, polysaccharides, and lipids).
• A common core of essential biochemical processes.

“Anything found to be true of E. coli

must also be true of elephants.”
-Jacques Monod

Source: Biochemistry: A Short Course. Permission: © 2015 Macmillan Education.

 The Foundations of Life
The living state can be considered from four different
perspectives or foundations:

• Chemical

• Energy

• Genetic

• Evolutionary
 Chemical Foundations

• All living things are made from

simple and common ingredients.
• Four elements (carbon, oxygen,
hydrogen, and nitrogen) account
for 98% of most organisms.
– Water accounts for much of the
oxygen and hydrogen in living
things.
– All known life forms are
carbon based.

“Given enough time, hydrogen starts to wonder

where it came from, and where it is going.”
 Chemical Foundations
-Gathering the Building Materials-
• Most of the chemical elements within the biosphere are
readily available:
– Carbon (from air through plants)
– Oxygen (from air)
– Hydrogen (from water)
• Air contains lots of nitrogen but in an inert form (N2).
• Ultimately, nitrogen within the biosphere comes from plants,
which extract it from soil.
• The availability of nitrogen in soil often limits growth of Fritz Haber
plants, limiting the amount of food we can produce.
• The amount of naturally occurring nitrogen in soil would
enable us to grow enough food for about 4 billion people.
 Chemical Foundations
-What are you worth?-

• In 1972, the U.S. Bureau of Chemistry and Soils calculated the

chemicals within a human body to be worth less than a dollar.

• However you are much more valuable than the sum of your base
parts.

• The tissues, organs, and biomolecules within a human being have

an estimated value of $45,000,000.

• While the chemical components of living things are not exotic,

how they come together is priceless.
 Chemical Foundations
-All Life (as we know it) is Carbon-Based-
• Carbon is extremely versatile in terms of the number and variety of
chemical bonds that it can form.

C C C

• This enables creation of a wide array of complex molecules, for example:

Amino acids Sugars Nucleotides

Source: Biochemistry: A Short Course. Permission: © 2015 Macmillan Education.
 Chemical Foundations
-All Life (as we know it) is Carbon-Based-

• Silicon is the “next-best” candidate as a chemical foundation for life.

• Also can form four covalent bonds
• Highly abundant in the Earth’s crust

• Why are we based in carbon rather than silicon?

• Carbon-to-carbon bonds are stronger than silicon-to-silicon bonds
(more stable biomolecules).
• More energy released on combustion of carbon-carbon bonds (more
energy from carbon-based nutrients).
• Combustion products of carbon (carbon dioxide) are soluble and
remain active in biosphere (recycling).
 Chemical Foundations
-Biomolecules Contain a Variety of Functional Groups-

Common Functional Groups

• Different functional groups are unique with respect to their size, shape,
charge, reactivities, and hydrogen-bonding capacity.
 Chemical Foundations
-Biomolecules Contain a Variety of Functional Groups-

• Functional groups exist in the context of biomolecules.

• The properties of the functional groups determine the structure,
function, and properties of the biomolecule.
 Chemical Foundations
-Structure-Function Relationship of Biomolecules-

• For all biomolecules, structure dictates function.

• Molecules do what they do because of their structures.

• A central goal of this course is to appreciate the structure-

function relationship of biomolecules.

• Understanding the structure-function relationship of biomolecules

allows one to predict molecular function, understand complex
biology (and pathobiology), and rationale development of
treatments.
 Chemical Foundations
-Structure-Function Relationship of Biomolecules-

• Conformation- flexible spatial arrangement of atoms within a

molecule (can be changed without breaking covalent bonds).

• Configuration- fixed spatial arrangement of atoms within a

molecule (cannot be changed without breaking covalent bonds).
– Configuration is conferred by either:
• Double bonds
• Chiral centers
 Chemical Foundations
-Configuration with Respect to Double Bonds-
• Geometric (cis-trans) isomers have the same chemical formula
but differ in the configuration of groups with respect to a non-
rotating double bond.
– Cis: “on this side” groups on the same side of the double bond.
– Trans: “across” groups on opposite sides of the double bond.

trans cis
 Chemical Foundations
-Configuration with Respect to Double Bonds-
• Geometric (cis-trans) isomers can have very different biological
properties.
• In later chapters, we will see the biological consequences of cis-
trans isomers in the context of proteins and lipids.

Protein cis trans isomers Lipid cis trans isomers

 Chemical Foundations
-Configuration with Respect to Chiral Carbons-
• A chiral carbon has four different substituents attached; these
groups may be arranged in different ways in space yielding two
stereoisomers that differ in their configuration.
• While the chemical properties of stereoisomers tend to be
identical, their biological properties are often distinct.
 Chemical Foundations
-Identifying Chiral Carbons-
• Identify all the chiral carbons of these molecules.
• Answers on next slide.
 Chemical Foundations
-Identifying Chiral Carbons-
• Chiral carbons are indicated by *.

*
* * *
* *
* *
 Chemical Foundations
-Biochemistry is Highly Stereospecific-
• The stereo specificity of biochemistry is apparent in the construction
and interactions of biomolecules.

• Construction: Biomolecules often constructed exclusively from

one stereoisomer. For example, proteins are built entirely from
L-Amino acids.

•• Interactions:
Interactions: Interactions
Interactions between
between biomolecules,
biomolecules, asas well
well asas
between biomolecules and small molecules, are stereospecific.
 Chemical Foundations
-Stereospecificity: Where Chemistry Meets Biology-
• Synthesis of chemical compounds (such as drugs) which have an
asymmetric carbons result in a mixture of all the chiral forms.
• These forms may have different biological activities.
• For example, thalidomide has two chiral forms, one of which causes
birth defects.
• Frances Kelsey, a Canadian physician working as a reviewer for the FDA,
saved countless children when she refused to approve thalidomide.

Dr. Francis Kelsey

https://en.wikipedia.org/wiki/Fran
Thalidomide ces_Oldham_Kelsey
 Chemical Foundations
-Complex Molecules from Simple Precursors-

• Biomolecules often polymers of simple building blocks.

• The structure and function of the resulting biomolecules are more
complex than their precursor molecules; the whole is greater than the
sum of the parts.
• Advantages of constructing biologicals as polymers:
• Simplicity: Simple and conserved reactions for synthesis and
degradation.
• Recycling: biomolecules can be digested back to component
building blocks which are reusable.
• Diversity: Incredibly complex molecules can be generated.
 Chemical Foundations
-Four Major Classes of Biomolecules-

• There are four major classes of biomolecules:

• Proteins
• Carbohydrates
• Nucleic Acids
• Lipids

• Within each category, we will learn the structures of the

building blocks, the nature of the linkages between building
blocks, the higher-order structures that are formed, and
biological functions of these molecules.
 Chemical Foundations
-Four Major Classes of Biomolecules (Proteins)-
• Proteins
• Linear polymers of amino acids.
• There are 20 different amino acids, including these examples:

• Amino acids link together to form linear chains that fold into
complex patterns with distinct biological activities.
 Chemical Foundations
-Four Major Classes of Biomolecules (Carbohydrates)-
• Polysaccharides
• Monosaccharides linked together to form linear or branched
polymers.
• These higher order polysaccharides serve many important biological
roles including structural, energy storage, and cellular recognition.
 Chemical Foundations
-Four Major Classes of Biomolecules (Nucleic Acids)-
• Nucleic Acids
• Linear polymers of nucleotide building blocks (5 building blocks for
DNA and RNA).
• Involved in all aspects storage and utilization of genetic information.
 Chemical Foundations
-Four Major Classes of Biomolecules (Lipids)-
• Lipids
• Lipids are aggregates (rather than defined polymers) of building
blocks.
• Lipids serve in energy storage, formation of membranes, and
signalling.
 Cellular Foundations
-Prokaryotes and Eukaryotes-
There are two basic classes of living organisms; prokaryotes and eukaryotes.

Prokaryotes
• Small (~ 1µm diameter), simple, single cell organisms (such as bacteria).

• Rapid growth allow quick adaptation to changing environmental conditions.

• A single compartment, the nucleoid, which contains nucleic acid. Other

biomolecules (proteins, metabolites, etc.) in a complex, organized mix.

Eukaryotes
• Large (~100 µm diameter) complex cells.

• Make up multi-cellular organisms such as yeast, plants, fungi, vertebrates.

• Organelles (nucleus, mitochondria, golgi, endoplasmic reticulum, etc) to support

specialized functions.

• Differentiation of cells to unique and specialized cell types.

 Cellular Foundations
-Blurred Lines (Prokaryote or Eukaryote?)-

• Your body contains ~30 trillion eukaryotic cells.

• You are also home to ~100 trillion prokaryotic cells.
• These prokaryotic cells are critical for our health.
– Bacteria in the gut help digest food and maintain a functional immune
system.
– Our second brain (the gut) including the microflora, may impact
mental health (depression, anxiety), obesity, and intelligence.
• Possible ways to influence the microbiota include diet, pro and
prebiotics, and fecal transplants.
 Cellular Foundations
-In vitro vs In vivo-
• Biomolecules undergo complex, organized interactions within the cell.
• Understanding these molecules and their interactions is a central challenge
of biochemistry.
• Studying molecules in isolation simplifies experiments but may be at the
expense of biological significance.
• In general, there are two experimental approaches:
• In vitro (in glass) studies the behaviour of molecules outside the context
of the cell and organism.
• In vivo (in the living) studies occur within the complexity of the cell or
organism.
• Experiments which are successful in vitro often fail in vivo.
 Energy Foundations

• Being alive is energetically expensive, this energy must be obtained

from the environment.
– To commercially purchase all of the energy (ATP) that your body
requires would cost about 4.5 million dollars/day.
• In BMSC230 you will study (in quantitative and chemical terms)
the means by which energy is extracted, channeled, and consumed
in living cells.
• In this course, we are more interested in the energetics of
biomolecular conformational changes as well understanding how
free energy contributes to reaction rates and equilibrium (enzymes).
• Cellular energy conversion can be considered in the context of the
laws of thermodynamics.
 Energy Foundations
-First Law of Thermodynamics-

• First Law of Thermodynamics: In any physical or chemical

change, the total amount of energy in the universe remains
constant, although the forms of the energy may change.
• Cells are highly effective transducers of energy, converting the
energy of metabolized nutrients, or the energy of the sun, into
work, heat, or the generation of complex biomolecules.
 Energy Foundations
-Second Law of Thermodynamics-

• Second Law of Thermodynamics: the tendency in nature is toward

ever greater disorder: the total entropy (disorder) of the universe is
continually increasing.
• However, living systems and their biomolecules require a high degree
of organization.
 Energy Foundations
-Gibbs Free Energy-
• Willard Gibbs developed the theory of energy changes during chemical
reactions.
• He demonstrated that the free energy (G) of any closed system can be
defined in terms of:

Enthalpy (H): reflects the number and kinds of bonds.

Entropy (S): The degree of randomness.
Temperature: In degrees Kelvin.

The definition of free energy is :

G = H - TS
Thus, the free energy change is:
DG = DH - TDS
 Energy Foundations
-The Meaning of Free Energy-

DG > 0
Non-spontaneous process, needs input of free energy to proceed.
endergonic

DG < 0
Spontaneous process, releases free energy which can be used to do
work; proceeds until equilibrium is reached.
exergonic

DG = 0
System is at equilibrium, there is no change in free energy in the
system.
 Energy Foundations
-Energy Coupling Links Reactions in Biology-
• Cells can drive thermodynamically unfavorable reactions by coupling
energy requiring (endergonic) to energy releasing (exergonic)
reactions.
• If the sum of the free energy changes is negative, then the overall
process is exergonic (spontaneous).
 Energy Foundations
-The Central Role of ATP in Metabolism-

• Energy extracted to the form of adenosine

triphosphate (ATP) which serves as a common
energy currency.
• ATP serves as the link between catabolic
reactions and anabolic reactions.

Source: Biochemistry: A Short

Course. Permission: © 2015
Macmillan Education.

ATP
 Genetic Foundations
• The perpetuation of life requires that genetic information be:
• stored in a stable form.
• expressed accurately in the form of gene products.
• reproduced with minimal errors.

• For many organisms, deoxyribonucleic acid (DNA) provides:

• the instructions for forming all other cellular components.
• a template for production of identical DNA molecules to be distributed
to the progeny when a cell divides.

Central Dogma of Biochemistry

 Genetic Foundations
-Structure of DNA Allows For Replication and Repair-

• The basic unit of DNA is two complimentary

strands.
• Each strand is a linear polymer of four different
types of building blocks.
• It is the linear sequence within the strands that
encodes information.

"It has not escaped our notice that the specific pairing we
have postulated immediately suggests a possible copying
mechanism for the genetic material.
Watson & Crick: Nature 171: 737-738 (1953)
 Genetic Foundations
-Linear Sequence in DNA Encodes Three-Dimensional
Protein Structures-

• The nucleotide sequence of genes

dictates the sequence of amino acids
incorporated into the corresponding
protein.
• The amino acid sequence of the
protein dictates its structure.
• The structure of the protein dictates
its biological activity.
 Evolutionary Foundations
-Changes in the Hereditary Instructions Allow Evolution-
• Random changes in genotype
(genetic information) can result in a
change in phenotype (observable
characteristics).
• If this change offers a survival
advantage it will be selected for
over time, if it disadvantages the
organism it will be selected against.

“Nothing in biology makes sense except

in the light of evolution.”
- Theodosius Dobzhansky
 Evolutionary Foundations
-The Ship of Theseus-

• If, over time, piece by piece, all of the pieces of a ship were
replaced, does it remain the same ship?
• Given the constant turnover of molecules within a living
organism, are you the same person you were in the past?
• Why does this process of regeneration need to stop?
 Copyright Sourcing
Images/Figures/Tables from Textbook – Permission: Courtesy of MacMillan Learning.

Slide 7: Source: https://en.wikipedia.org/wiki/Fritz_Haber#/media/File:Fritz_Haber.pngb Permission: Public Domain. Courtesy of The Nobel Foundation.

Slide 11: Source: Lehninger Principles of Biochemistry (2008) 5th Edition, page 12. Permission: This material has been reproduced in accordance with the
University of Saskatchewan Fair Dealing Guidelines, an interpretation of Sec.29.4 of the Copyright Act.

Slide 12: Source: Lehninger Principles of Biochemistry (2008) 5th Edition, page 13. Permission: This material has been reproduced in accordance with the
University of Saskatchewan Fair Dealing Guidelines, an interpretation of Sec.29.4 of the Copyright Act.

Slide 15: Source: https://en.wikipedia.org/wiki/Cis–trans_isomerism Permission: CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0/) Courtesy of

JaGa.

Slide 20: Source: Lehninger Principles of Biochemistry (2008) 5th Edition, page 19. Permission: This material has been reproduced in accordance with the
University of Saskatchewan Fair Dealing Guidelines, an interpretation of Sec.29.4 of the Copyright Act.

Slide 21a: Source: https://en.wikipedia.org/wiki/Thalidomide#/media/File:Thalidomide_enantiomers.svg Permission: Public Domain. Courtesy of Vaccinationist.

Slide 21b: Source: https://en.wikipedia.org/wiki/Frances_Oldham_Kelsey#/media/File:Frances_Oldham_Kelsey_and_John_F._Kennedy.jpg Permission: Public

Domain.

Slide 29: Source: http://www.pinsdaddy.com/bacteria-friend_XFwpXrdgdZCJTyoa6yobl5aR0tLZDG04K9ney51XJms/ Permission: This material has been

reproduced in accordance with the University of Saskatchewan interpretation of Sec.30.04 of the Copyright Act.

Slide 36: Source: Lehninger Principles of Biochemistry (2008) 5th Edition, page 23. Permission: This material has been reproduced in accordance with the
University of Saskatchewan Fair Dealing Guidelines, an interpretation of Sec.29.4 of the Copyright Act.

Slide 37: Source: Lehninger Principles of Biochemistry (2008) 5th Edition, page 26. Permission: This material has been reproduced in accordance with the
University of Saskatchewan Fair Dealing Guidelines, an interpretation of Sec.29.4 of the Copyright Act.

Slide 40: Source: Lehninger Principles of Biochemistry (2008) 5th Edition, page 29. Permission: This material has been reproduced in accordance with the
University of Saskatchewan Fair Dealing Guidelines, an interpretation of Sec.29.4 of the Copyright Act.

Slide 41: Source: Lehninger Principles of Biochemistry (2008) 5th Edition, page 29. Permission: This material has been reproduced in accordance with the
University of Saskatchewan Fair Dealing Guidelines, an interpretation of Sec.29.4 of the Copyright Act.